Unraveling metalloproteinase function in skeletal biology and disease using genetically altered mice

The metalloproteinase family includes MMP, ADAM and ADAMTS proteases. Mice deficient in individual or pairs of metalloproteinases have been generated, and a number of these genetic models spontaneously develop skeletal abnormalities. Here we review metalloproteinase function in endochondral and intramembranous ossification, as well as in postnatal bone remodeling. We highlight how metalloproteinases enable interactions between distinct bone cell types and how this communication contributes to the skeletal phenotypes observed in knockout mice. In addition to the physiological actions of metalloproteinases in the skeletal system, the experimental manipulation of metalloproteinase-deficient mice has revealed substantial roles for these enzymes in osteoarthritis and rheumatoid arthritis. MMP, ADAM and ADAMTS proteases thus emerge as key players in the development and homeostasis of the skeletal system.